1. Field of the Invention
The present invention relates to pharmaceutically active pteridine derivatives, which have an antiarrhythmic, diuretic and cardioprotective efficacy.
2. Discussion of the Background
Specific classes of substances with the pteridine structure have proven to be pharmaceutically efficacious. In pharmaceutical practice the 2,4,7-triamino-6-phenylpteridine (Triamterene) plays a prominent role as an anti-potassium uretic drug (U.S. Pat. No. 3,081,230: cf. E. Mutschler and H. Knauf, 30 Jahre Triamteren, Wissenschaftsverlag Koln, 1984). Broad-scale investigations have been devoted to the correlation between the structure and the effect in the pteridine class. Thus, Weinstock and Wiebelhaus investigated more than 500 pteridine derivatives. (Cf. K. Fellinger, Therapie mit Triamteren 21). However, with respect to their general acceptance, the conclusions that were drawn have not remained unrefuted. (Cf. E. Mutschler et al., loc. cit., pp. 11-18). The original concept, that compounds having the groups that are sterically less demanding, is no longer valid since it has now been shown that Triamterene derivatives which are substituted in the para position of the phenyl ring with a hydrophilic group have pharmaceutical utility (cf. U.S. Pat. No. 4,118,492, DE-A pharmaceutical agents are known as disclosed in U.S. Pat. No. 4,621,085 and/or the DE-A 34 12 765 which contain, as the active substance, a Triamterene derivative, whose 6-phenyl group is substituted lipophilically in the para position. Fluorine, chlorine, branched or cyclic alkyl having 3 to 6 carbon atoms, the benzyl-, trifluoromethyl or the nitro groups are cited as such lipophilic substituents.
German patent application p 37 40 441 (unpublished) shows compounds which are substituted para benzyltriamterene which has substituents both on the benzyl ring and at the benzylic carbon atom. The teaching of this application, however, does not point beyond the use of substituted derivatives of benzyltriamterene. If this prior art information is combined, the finding of G. H. Mudge (in Goodman-Gilman, The Pharmacological Basis of Therapeutics, 5th ed. McMillan Publishing Co., p 838) on the topic of Triamterene can still claim to be valid today: "It is a pteridine compound related chemically to folic acid. The diuretic activity of closely related homologues of Triamterene has been established but no specific structural requirements have been established."
Despite the excellent efficacy of some pharmaceutical active substance belonging to the pteridine class (This applies in particular to the Triamterene), there has still been a demand for active substances, which, with preferably greater hydrophilicity, maintain a therapeutic index that is at least just as good as Triamterene. Furthermore, it has been desirable to reduce the quantity of foreign substances subject to different metabolic processes and introduced to the organism. Correspondingly the goal has been to provide compounds useful in the smallest possible concentrations which exhibit a minimum of side effects. In addition, the related metabolic processes should be transparent and the secondary effects should be as straightforward and safe as possible.